Ranadheer Manthri1, Tejonath Gadepalli2, Deepthi Pathapati3, Vvs Prabhakar Rao3. 1. Department of Nuclear Medicine, Sri Venkateshwara, Institute of Medical Sciences, Tirupati, Andhra Pradesh, India. 2. Department of Nuclear Medicine, Care Hospitals, Hyderabad, Telangana, India. 3. Department of Nuclear Medicine, OMEGA Hospitals, Hyderabad, Telangana, India.
Abstract
Skeletal scintigraphy with 99mTc-methylene diphosphonate and 18-fluorine-fluoride the main stay in cancer follow-up for early detection of skeletal metastasis often reveal confusing and conflicting findings requiring proper interpretation in conjunction with clinical-radiological correlation. A series of commonly encountered findings are presented for elucidation.
Skeletal scintigraphy with 99mTc-methylene diphosphonate and 18-fluorine-fluoride the main stay in cancer follow-up for early detection of skeletal metastasis often reveal confusing and conflicting findings requiring proper interpretation in conjunction with clinical-radiological correlation. A series of commonly encountered findings are presented for elucidation.
Skeletal scintigraphy with 99mTc-methylene diphosphonate (99mTc-MDP) and 18-fluorine (18F)–fluoride is a sensitive and easy screening modality in the early detection of skeletal metastasis.[1] Osseous metastasis detection forms the single largest indication of skeletal scintigraphy. In the course of the investigation, a number of interesting and intriguing scan’ features crop up challenging the final outcome. Identification, analysis, radiological, and clinical correlation are essential to obviate misinterpretation.
Locational Importance of the Abnormality
Solitary 99mTc-MDP/18F–fluoride avid focus in the spine is challenging in its interpretation being metastatic, traumatic, or degenerative. Skeletal scintigraphic screening in a known case of carcinoma for evidence of any metastasis reveals a solitary intensely avid distinctly focal uptake in left pedicle 12th dorsal vertebra with conspicuously absent radiographic abnormality on plain radiography or computerized tomography (CT) on bone window [Figure 1]. Focal uptake in the pedicles even with no evidence on CT at all times is to be considered as metastasis.[23] Earliest pedicle localization is due to the hematogenoeus spread of the tumor cells localizing first in that region being the junctional site of vessels, entering from the pedicles, and arborising into the posterior elements and vertebral body. Scintigraphic localization is more sensitive and earlier than radiological abnormality. Therefore, a solitary focal uptake in the pedicle on 99mTc-MDP scan is diagnostic of metastasis despite absence of radiological abnormality.
Figure 1
Skeletal scintigraphy showing a solitary intensely avid focal uptake in left pedicle D12 vertebra (arrow) with no computerized tomography abnormality on bone window (dotted arrow)
Skeletal scintigraphy showing a solitary intensely avid focal uptake in left pedicle D12 vertebra (arrow) with no computerized tomography abnormality on bone window (dotted arrow)
Implication of Long Bone Medullary Uptake
Occasionally, while reviewing the whole body sweep of 99mTc-MDP/18F–fluoride scan a linearly oriented uptake of variable intensity ranging from faint to intense avidity will be seen in the central medullary diaphysial region of long bones, especially femur preempting to be labeled as metastasis [Figure 2a]. Plain radiography and CT bone window will show a lacy area of sclerosis in the medullary region confined to the fatty marrow sparing the cortex[45] [Figure 2b]. Such nonspecific focal uptake is the result of old healed calcified medullary infarcts of protean etiology, most often incriminating causes such as steroid ingestion, pancreatitis, alcoholism, and trauma are lacking and patient asymptomatic. Interpretation of such pattern recognition as plausible medullary bone infarct is aided by the lesion's diaphysial calcified fat marrow location and clinical-radiological correlation.
Figure 2
(a) Skeletal scintigraphy showing solitary intensely avid focal uptake in the central medullary distal diaphysial region of left femur excluding the cortex (arrow). (b) Plain radiography anterior-posterior, lateral, and computerized tomography bone window left femur showing lacy area of sclerosis with specks of calcification in the medullary region confined to the fatty marrow sparing the cortex (arrow) typical of old healed medullary bone infarct
(a) Skeletal scintigraphy showing solitary intensely avid focal uptake in the central medullary distal diaphysial region of left femur excluding the cortex (arrow). (b) Plain radiography anterior-posterior, lateral, and computerized tomography bone window left femur showing lacy area of sclerosis with specks of calcification in the medullary region confined to the fatty marrow sparing the cortex (arrow) typical of old healed medullary bone infarct
Hyper Avid Hypertrophied Osteoblastic Lesions
Elderly males of known malignancy during follow-up or metastatic work up often reveal a very highly intense uptake on 18F–fluoride scan involving the entire vertebra, large contiguous areas of hemi pelvis, long segment shaft of long bones with enlargement [Figure 3a]. Radiological and CT features of coarse disorganized densely sclerotic trabeculations [Figure 3b], close mimic of such lesions is osteoblastic skeletal metastasis of prostatic origin; however, the lead in these lesions is the male predilection, 18F–fluoride hyperavidity, expansion of bones, intense coarse sclerosis on radiography[6] (bigger and brighter bones), symptom-free clinical state despite the extent and intensity of skeletal lesions.
Figure 3
(a) Very highly intense uptakes on 18F–fluoride scan involving the entire D4 and L5 vertebrae, large contiguous area of left hemi pelvis, long segment proximal shaft of left tibia (arrows). (b) Computerized tomography bone window images pelvis showing dense coarsely sclerotic lesions (dotted arrows) classical of Paget's disease of bone
(a) Very highly intense uptakes on 18F–fluoride scan involving the entire D4 and L5 vertebrae, large contiguous area of left hemi pelvis, long segment proximal shaft of left tibia (arrows). (b) Computerized tomography bone window images pelvis showing dense coarsely sclerotic lesions (dotted arrows) classical of Paget's disease of bone
Nonosseous Metastatic Localization of 99mTc-Methylene Diphosphonate
Osteoscarcoma of bone usually metastasizes to lungs, lymph nodes, and rarely to bones. The minimum workup for primary metastases generally includes CT of the chest and whole-body bone scintigraphy. In a known case of Osteosarcoma right femur, 99mTc-MDP skeletal scintigraphy revealed heterogeneously avid uptake in the primary site at left femur and additionally in lungs bilaterally [Figure 4]. The role of skeletal scintigraphy is more to detect extra osseous metastasis than osseous ones.[78] 99mTc-MDP localization in the lung metastasis is in conformity with the tissue characteristics of the primary osteoblastic nature of the osteoscarcoma resulting in the pulmonary metastasis taking up the bone-seeking radionuclide.
Figure 4
Known case of osteoscarcoma right femur 99mTc-methylene diphosphonate skeletal scintigraphy revealing a large heterogeneously avid uptake in the primary site at lower shaft of left femur (arrow) and additionally soft tissue deposits in bilateral lung parenchyma (dotted arrows)
Known case of osteoscarcoma right femur 99mTc-methylene diphosphonate skeletal scintigraphy revealing a large heterogeneously avid uptake in the primary site at lower shaft of left femur (arrow) and additionally soft tissue deposits in bilateral lung parenchyma (dotted arrows)
18-Fluorine Fludeoxyglucose, 99mTc-Methylene Diphosphonate Mismatch in Early Lytic Metastatic Lesions
Higher sensitivity and early detection rate of 99mTc-MDPosteoblastic metastasis is well established due to larger and rapid incorporation of the tracer into the hydroxyapatite lattice of the osteoblastic lesions the same does not hold good for rapidly multiplying lytic lesions with little osteoblastic or osteosclerotic reparative reaction time.[9] 18F-fludeoxyglucose positron emission tomography/CT instead by its incorporation in the hypermetabolic areas of rapidly mitotic lytic lesions of the bone shows an intense uptake [Figure 5a] with a distinct nonavid 99mTc-MDP localization[10] [Figure 5b].
Figure 5
(a) 18F-fludeoxyglucose computerized tomography showing localization in hyper metabolic primary lung lesion and rapidly mitotic lytic skeletal metastasis (arrows). (b) Maximum intensity projection image of 18F-fludeoxyglucose positron emission tomography/computerized tomography showing metabolically active primary lung mass (arrow) and multiple disseminated metabolically active skeletal lesions (dotted arrows) with 99mTc-methylene diphosphonate skeletal scintigraphy whole body sweep not showing any abnormal avid uptake in the corresponding areas
(a) 18F-fludeoxyglucose computerized tomography showing localization in hyper metabolic primary lung lesion and rapidly mitotic lytic skeletal metastasis (arrows). (b) Maximum intensity projection image of 18F-fludeoxyglucose positron emission tomography/computerized tomography showing metabolically active primary lung mass (arrow) and multiple disseminated metabolically active skeletal lesions (dotted arrows) with 99mTc-methylene diphosphonate skeletal scintigraphy whole body sweep not showing any abnormal avid uptake in the corresponding areas
Entity of Occult Subchondral Femoral Head Fractures
Hip joint being the largest weight bearing joint often reveals uniform or focal 99mTc-MDP, uptake either unilateral or bilateral, especially in a carcinoma follow-up situation needs a pragmatic approach and interpretation. Despite absence of any cognizable or revealed injury, unrecognized stress induced subclinical trauma results in occult subchondral femoral head fractures which on skeletal scintigraphy show up as diffuse uptake in the femoral head and neck region and mimic infection or tumor[11] [Figure 6a]. MRI answers the issue with the classical features of subchondral fracture separating from metastasis[1213] [Figure 6b].
Figure 6
(a) Case of carcinoma breast follow-up with no history of trauma 99mTc-methylene diphosphonate skeletal scintigraphy revealing diffuse uptake in the femoral head and neck region (arrow). (b) Axial short tau inversion recovery weighted image of left hip joint showing hyperintense area in medial aspect of head of femur (arrow) and corresponding axial T2-weighted image showing mild flattening of femoral head contour (dotted arrow)
(a) Case of carcinoma breast follow-up with no history of trauma99mTc-methylene diphosphonate skeletal scintigraphy revealing diffuse uptake in the femoral head and neck region (arrow). (b) Axial short tau inversion recovery weighted image of left hip joint showing hyperintense area in medial aspect of head of femur (arrow) and corresponding axial T2-weighted image showing mild flattening of femoral head contour (dotted arrow)
Conclusion
Skeletal scintigraphy has a distinct niche in early detection of osseous metastases due to its superior sensitivity over plain radiography, CT. However, a host of nonmetastatic clinical situations is often revealed during skeletal scintigraphy necessitating a pragmatic approach considering the clinical, radiological, and historical correlation.